[18F]fluoride is produced by irradiation of water, containing H218O, with protons resulting in the reaction 18O(p,n)18F. Only a minor fraction of the [18O] is converted. The [18F]isotope is then separated from the water and processed for production of a radio-pharmaceutical agent.
In the current practice, fluoride recovery is based on the use of an anion-exchange resin. The recovery is carried out in two steps, extraction and elution: first the anions (not only fluoride) are separated from the enriched [18O]water and trapped on the said resin (Coenen et al., J. Labelled Compd. Radiopharm., 1986, vol. 23, pp. 455-467). The anions, including [18F]fluoride, are then eluted into a mixture containing water, organic solvents, an activating agent or phase transfer agent or phase transfer catalyst, such as for example the complex potassium carbonate-Kryptofix 222 (K2CO3-K222) or a tetrabutylammonium salt. The [18F]fluoride radiochemical recovery yield is very effective, usually exceeding 99%.
The most usual labelling method, known as nucleophilic substitution, requires anhydrous or very low water content solutions. Thus, an evaporation step (or drying step) is still necessary after [18F]fluoride recovery to remove the excess water. It usually consists in multiple azeotropic evaporations with acetonitrile or low boiling temperature organic solvent. Such evaporations require several minutes (Schlyer et al., Appl. Radiat. Isot., 1990, vol. 40, pp. 1-6).
The current trend in the automation of the preparation of radiopharmaceuticals for medical imaging is to develop “Lab-on-chip” devices. The aforementioned evaporation step is very difficult to implement within such a “Lab-on-chip” device.
In document D. M. Jewett et al, Extraction of [18F]Fluoride from [18O] Water by a Fast Fibrous Anion Exchange Resin, Radiat. Isot. Vol. 41, No. 6, pp. 583-586, 1990, [18F]fluoride for nucleophilic radiofluorination was recovered from target water by trapping on a fibrous anion exchange resin in the hydroxide form and subsequent displacement into wet methanolic K2CO3. Extraction into methanol facilated rapid evaporation and resolubilization in the [18F]fluoride as an ion pair.
Document CN 1 887 829 A discloses, in the field of chemical synthesis, a process for synthesizing [18F] labeled positive electron radioactive tracer with ionic liquid as phase transfer catalyst. The process includes the following steps: 1. transferring [18F] ion from cyclotron to accepting bottle and leading to anion exchange column; 2. eluting [18F] ion in the column with alkaline weak acid salt, acetonitrile and ionic liquid, and conveying to reactor bottle; 3. dissolving the precursor in acetonitrile, adding to the reactor bottle and heating; 4. cooling and regulating pH value; and 5. separating and collecting the target product from the solution.